Hippocampus-Sparing Whole-Brain Radiotherapy: Dosimetric Comparison Between Non-Coplanar and Coplanar Planning

Original Article Page 1 of 11

Hippocampus-sparing whole-brain radiotherapy: dosimetric comparison between non-coplanar and coplanar planning

Li-Jhen Chen1, Ming-Hsien Li1,2, Hao-Wen Cheng1,3, Chun-Yuan Kuo1,3, Wei-Lun Sun1, Jo-Ting Tsai1,2

1Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; 2Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan Contributions: (I) Conception and design: LJ Chen, MH Li; (II) Administrative support: JT Tsai; (III) Provision of study material or patients: JT Tsai, MH Li; (IV) Collection and assembly of data: LJ Chen, CY Kuo, HW Cheng, WL Sun; (V) Data analysis and interpretation: LJ Chen, CY Kuo, HW Cheng; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Jo-Ting Tsai, MD, PhD. Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Rd., Zhonghe Dist., New Taipei City 235, Taiwan. Email: [email protected].

Background: To compare non-coplanar and coplanar volumetric-modulated arc therapy (VMAT) for hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) using the Elekta Synergy and Pinnacle treatment planning system (TPS) according to the suggested criteria of the radiation therapy oncology group (RTOG) 0933 trial. Methods: Nine patients who underwent WBRT were selected for this retrospective study. The hippocampus was contoured, and the hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus for each patient. Non-coplanar and coplanar VMAT plans were generated for each patient. All treatment plans were generated for a prescribed dose (PD) of 30 Gy in 10 fractions. Results: The average volumes of the hippocampus and hippocampal avoidance region were 2.8±0.38 and 3 27±2.48 cm , respectively. For coplanar and non-coplanar VMAT plans, the average D100% of the hippocampus was 8.60 Gy (range, 8.30–8.80 Gy) and 8.56 Gy (range, 8.30–8.90 Gy), respectively, and the average

Dmax of the hippocampus was 15.29 Gy (range, 14.35–15.92 Gy) and 14.99 Gy (range, 13.80–15.83 Gy),

respectively. The non-coplanar VMAT plans showed a significantly lower average maxD of the lens (4.23 Gy) than did the coplanar VMAT plans (4.77 Gy). The average gamma passing rate for non-coplanar and coplanar VMAT quality assurance (QA) with criteria of 3%/3 mm were 95.4%±2.6% and 95.6%±1.6%, indicating good agreement between the calculated plan dose and the measured dose. Conclusions: We showed that the suggested criteria of the RTOG 0933 trial for the hippocampal dose can be achieved in both coplanar and non-planar VMAT plans. We performed VMAT QA for each treatment plan to verify the clinical feasibility.

Keywords: Hippocampus; RTOG 0933; radiation therapy; volumetric-modulated arc therapy (VMAT); whole brain

Received: 10 July 2020; Accepted: 25 January 2021; Published: 30 March 2021. doi: 10.21037/tro-20-50 View this article at: http://dx.doi.org/10.21037/tro-20-50

Introduction patients and 4–6 months in treated patients (2). Many cancer patients will eventually develop brain metastases, and Brain metastases are the most common intracranial tumors the standard therapeutic approaches for patients with brain in adults and occur in 10–30% of cancer patients (1). The metastasis include surgery and radiotherapy. Whole-brain prognosis of patients with brain metastases is generally radiotherapy (WBRT) has been implemented in clinical poor, with a median survival time of one month in untreated practice for decades. In general, patients with oligo-brain

© Therapeutic Radiology and Oncology. All rights reserved. Ther Radiol Oncol 2021;5:1 | http://dx.doi.org/10.21037/tro-20-50 Page 2 of 11 Therapeutic Radiology and Oncology, 2021 metastasis undergo surgical resection, chemotherapy and the treatment (14). Therefore, the purpose of this study is stereotactic radiosurgery (SRS) alone or SRS combined with to compare the non-coplanar and coplanar VMAT for HA- WBRT (3). For patients with multiple brain metastases, WBRT using the Elekta Synergy (Elekta AB) and Pinnacle WBRT is a commonly used treatment modality; however, (Philips Medical System, Fitchburg, WI, USA) TPS SRS seems to be a new standard option (4). according to the suggested criteria of the RTOG 0933 trial. WBRT plays an important role in tumor control for We also performed VMAT quality assurance (QA) for each patients with multiple brain tumors and thus lower the treatment plan to evaluate the feasibility of HA-WBRT subsequent neurological death. WBRT is also used in with different VMAT techniques. prophylactic cranial irradiation for patients with small We present the following article in accordance with cell lung carcinoma (5-7). Although WBRT was proven the MDAR reporting checklist (available at http://dx.doi. to be effective in eliminating brain tumors, damage to org/10.21037/tro-20-50). normal brain tissue is inevitable, and several complications have been observed following treatment that decreases Methods the quality of life of patients (8). Previous studies showed that poor neurocognitive function may occur months Patient selection and delineation after radiotherapy due to radiation-induced hippocampal damage. The radiation-induced hippocampal damage causes The study was approved by the Taipei Medical University a decline in neurocognitive function, including deficiencies Joint Institutional Review Board, and the IRB number in learning, memory and spatial management, which can be is TMU-JIRB No. N201711047. Nine patients with observed in patients. The clinical symptoms of radiation- brain metastases outside 5 mm of the hippocampus who induced hippocampal damage include memory loss, lack of underwent WBRT were selected for this retrospective concentration, and emotional disorders (9,10). study. Computed tomography (CT) and magnetic The findings of radiation therapy oncology group resonance (MR) images were used for each patient to (RTOG) 0933 trial suggest that hippocampal avoidance delineate the hippocampus, hippocampal avoidance regions during WBRT (HA-WBRT) could reduce radiation- (defined as the hippocampus with an expansion of 5-mm induced neurocognitive toxicities (11). The purpose of HA- margin) according to the RTOG 0933 trial, optic nerves, WBRT is to generate hippocampal avoidance regions while optic chiasm, and lens. CT images (3 mm slice thickness) allowing the sufficient prescribed dose (PD) to cover the for treatment planning were generated using a Phillips remainder of the brain. HA-WBRT can significantly reduce 16 slice CT scanner (Brilliance CT Big Bore). All 6-MV 3 the hippocampal dose. Although the risk of developing VMAT plans were optimized with Pinnacle Version 14 subsequent brain metastasis after HA-WBRT is unknown, for Elekta Synergy with 40 multileaf collimator (MLC) leaf Ghia et al. (12) reported that of 272 cases with brain pairs (MLCi) of 1 cm leaf width at isocenter. metastases, the incidence of metastases within 5 mm of the The study was conducted in accordance with the perihippocampal region was low (3.3%). Thus, their results Declaration of Helsinki (as revised in 2013). The study indicated that a 5-mm margin around the hippocampus was approved by the Taipei Medical University Joint for HA-WBRT was an acceptable risk. With advances in Institutional Review Board (TMU-JIRB No. N201711047), radiotherapy, several reports have discussed the application and informed consent was taken from all the patients. of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for HA-WBRT Planning technique and attempted to minimize WBRT-induced neurocognitive toxicities. Nevelsky et al. (13) evaluated the feasibility of According to the RTOG 0933 trial, the clinical target the RTOG 0933 trial using the Elekta Infinity (Elekta AB, volume (CTV) was defined as the whole brain parenchyma Stockholm, Sweden) equipped with Monaco 3.1 (Elekta AB, to C1, and the planning treatment volume (PTV) was Stockholm, Sweden) treatment planning system (TPS) to defined as the CTV excluding the hippocampal avoidance perform IMRT with seven coplanar plus two non-coplanar regions in this study. A total dose of 30 Gy in 10 fractions beams. VMAT, with continuous gantry rotation and leaf was prescribed to the PTV. All plans in this study aimed to motion with a varying dose rate, can increase treatment cover at least 90% of the PTV by the PD. The following efficiency and reduce the amount of patient motion during dose constraints, which are summarized in Table 1, were

Table 1 RTOG 0933 compliance criteria and critical structure including one partial arc (PA) with a collimator angle of 45° constraint and couch angle of 70° and four FAs (clockwise for two FAs Variation Deviation Parameter Per protocol and counterclockwise for two FAs), were used (Table 2). acceptable unacceptable

PTV D2% ≤37.5 Gy D2% >37.5 Gy, V30Gy <90% Plan evaluation ≤40 Gy

D98% ≥25 Gy D98% <25 Gy D2% >40 Gy For the organs at risk (OARs) and PTV, the following

parameters were evaluated: PTV D2%, PTV D98%, D100% Hippocampus D100% ≤9 Gy D100% ≤10 Gy D100% >10 Gy and Dmax of the hippocampus, and Dmax of the optic chiasm Dmax ≤16 Gy Dmax ≤17 Gy Dmax >17 Gy and lens. The dosimetric parameters, including PTV V100

D2%, maximum dose to 2% volume, D98%, minimum dose to 98% (PTV VX is the percent volume of PTV covered by X% of

100% max volume; D , dose to 100% volume; D , maximum dose; the PD), PTV V95, homogeneity index (HI) and conformity V30Gy, percent volume covered by 30 Gy. index (CI) for the PTV, were evaluated. The HI is defined as follows (recommended by the ICRU 83) (15): Table 2 Gantry, collimator, and couch angles for the coplanar and HI = (D − D )/D non-coplanar VMAT beam arrangements 2% 98% median where Dmedian is the median dose of the PTV. Gantry Collimator Couch Beam name The CI is defined as follows (16): (degree) (degree) (degree) 2 CI = (PTV V95%) /(VPTV × V95) Coplanar beam arrangement where VPTV is the volume of PTV, and V95 is the volume V1 CW181-180 45 0 covered by 95% of the PD. V2 CCW180-181 45 0 The beam-on time was defined as the treatment time excluding the time for patient setup and couch rotation. V3 CW181-180 45 0 The beam-on times for different VMAT plans were V4 CCW180-181 45 0 reported and evaluated. The VMAT QA procedures were Non-coplanar beam arrangement completed for each plan and performed by measuring the

V1 CW181-180 45 0 dose distribution using the PTV 2D-array seven29 with a plane matrix of 27×27 air-filled ion chambers (17). V2 CCW180-181 45 0

V3 CW181-180 45 0 Statistical analysis V4 CCW180-181 45 0 The Wilcoxon signed-rank test was used for statistical V5 CW190-310 330 70 analysis among different VMAT techniques. A P value of CW, clockwise; CCW, counterclockwise; VMAT, volumetric- ≤0.05 was considered statistically significant. modulated arc therapy.

Results used in optimization: maximum dose to 2% of the PTV The basic characteristics of the nine patients are listed (PTV D2%) ≤37.5 Gy; minimum dose to 98% of the PTV in Table 3. The average volume of the hippocampus was (PTV D ) ≥25 Gy; D (D : the dose to X% of the 98% 100% x% 2.80 cm3 (range, 2.32–3.40 cm3), the average volume of the volume) and maximum dose (D ) of the hippocampus ≤9 max hippocampal avoidance region was 27.09 cm3 (range, 24.76– Gy and ≤16 Gy; D of the optic chasm and optic nerve 3 max 31.26 cm ), and the average volume of the whole brain was <37.5 Gy; and doses to the lens and optic nerve as low as 1,314.35 cm3 (range, 1,116.01–1,479.70 cm3). possible. The non-coplanar and coplanar VMAT plans In all treatment plans, the dose constraints for the were generated for each patient. For the coplanar VMAT hippocampus according to the RTOG 0933 trial were plans, four full arcs (FAs) (clockwise for two FAs and prioritized while limiting the dose to the lens. Figure 1 counterclockwise for two FAs) were used with a collimator shows the isodose lines (ranging from 1,500 to 3,400 cGy) angle of 45°. For the non-coplanar VMAT plans, five arcs, around the hippocampus of the non-coplanar and coplanar

Table 3 Basic characteristics of nine patients

Hippocampal Hippocampal 3 Patient Gender Primary site 3 3 Whole brain (cm ) volume (cm ) avoidance region (cm )

1 M Lung 2.71 25.23 1,282.31

2 M Lung 2.82 24.76 1,306.77

3 M Lung 2.40 25.44 1,479.70

4 M Liver 3.21 29.16 1,412.52

5 F Breast 3.40 31.26 1,262.58

6 M Lung 2.32 26.49 1,293.14

7 M Lung 2.37 25.70 1,322.27

8 F Lung 3.02 25.38 1,116.01

9 F Lung 2.96 30.39 1,353.86

Mean ± SD 2.80±0.39 27.09±2.48 1,314.35±101.33

Figure 1 Isodose distributions in axial, sagittal, and coronal views for representative hippocampal sparing WBRT using coplanar VMAT (A1– A3) vs. non-coplanar VMAT (B1–B3) in patient 7. Yellow-green contours indicate the right hippocampus, and light-blue contours indicate the left hippocampus. WBRT, whole-brain radiotherapy; VMAT, volumetric-modulated arc therapy.

DVH 100 90 80 70 60 Hippocampus non-coplanar 50 Lens non-coplanar PTV non-coplanar 40

Volume (%) Volume Hippocampus coplanar 30 Lens coplanar PTV coplanar 20 10 0 0 5 10 15 20 25 30 35 Gy

Figure 2 Comparison of the DVHs between the coplanar VMAT and non-coplanar VMAT plans. DVH, dose volume histograms; VMAT, volumetric-modulated arc therapy; PTV, planning treatment volume.

Table 4 Comparison of dosimetric parameters for OARs with P values Hippocampus Lens, Dmax (Gy) Optic chiasm, Dmax (Gy) Patient Dmax (Gy) Dmin (Gy)

Coplanar Non-coplanar Coplanar Non-coplanar Coplanar Non-coplanar Coplanar Non-coplanar

1 14.70 15.22 8.80 8.90 4.72 3.72 32.65 32.77

2 15.34 14.43 8.54 8.33 3.99 4.36 34.72 34.08

3 15.44 15.40 8.53 8.54 5.50 5.07 33.38 33.59

4 15.68 15.28 8.69 8.36 4.49 4.07 33.54 34.26

5 15.92 15.22 8.61 8.30 5.32 4.62 33.91 34.18

6 14.35 14.05 8.30 8.88 4.64 4.24 35.04 35.67

7 14.99 13.80 8.51 8.53 4.56 3.68 32.64 33.15

8 15.87 15.83 8.24 8.77 4.77 3.65 32.69 32.71

9 15.30 15.76 8.74 8.44 4.95 4.68 33.67 35.08

Mean ± SD 15.29±0.52 14.99±0.73 8.60±0.18 8.56±0.23 4.77±0.45 4.23±0.5 33.58±0.87 33.94±1.00

P value 0.173 0.953 0.015* 0.066 *, P<0.05.

VMAT plans on axial, coronal, and sagittal images from one coplanar VMAT plans, but the difference was nonsignificant case of this study. The average DVHs of the hippocampus, (P>0.05): coplanar VMAT =15.29 Gy (range, 14.35– lens and PTV for the non-coplanar and coplanar VMAT 15.92 Gy) and non-coplanar VMAT =14.99 Gy (range, plans for nine patients are shown in Figure 2. 13.80–15.83 Gy). The average D100% values of the hippocampus for the coplanar and non-coplanar VMAT plans were 8.60 Gy (range, 8.30–8.80 Gy) and 8.56 Gy Dose to OARs (range, 8.30–8.90 Gy), respectively. The non-coplanar

Table 4 shows the dose to the OARs for the non-coplanar VMAT plans showed a significantly lower average maxD of and coplanar VMAT plans. The non-coplanar VMAT the lens (P<0.05) than the coplanar VMAT plans: coplanar plans had a lower mean Dmax of the hippocampus than the VMAT =4.77 Gy (range, 3.99–5.50 Gy) and non-coplanar

VMAT =4.23 Gy (range, 3.65–5.07 Gy). The dose to the

0.01 optic chiasm for all plans did not exceed 37.5 Gy. ± 0.76 0.75 0.75 0.73 0.73 0.74 0.77 0.73 0.73 Non- coplanar 0.74

CI PTV dosimetry , percent volume volume , percent The PTV D2%, PTV D98%, PTV V30Gy (the percent volume 0.75 0.75 0.73 0.74 0.74 0.74 0.78 0.73 0.74 95% Coplanar

0.74±0.02 of PTV covered by 30 Gy), PTV V95, target coverage,

HI and CI are shown in Table 5. The average PTV D2%,

PTV D98%, and PTV V30Gy for the non-coplanar and 0.03 ± by 30 Gy; V

0.22 0.23 0.31 0.27 0.27 0.23 0.23 0.24 0.27 coplanar VMAT plans were 33.46±0.68 and 33.19±0.47 Gy, Non- coplanar 0.25 25.49±0.48 and 25.68±0.63 Gy, and 92.99%±0.35% and HI 92.57%±0.80%, respectively. 0.2 0.24 0.29 0.24 0.24 0.25 0.19 0.24 0.26 Coplanar 0.24±0.03 Beam-on time and VMAT QA

The beam-on time and VMAT QA results for nine patients are shown in Table 6. There was no significant difference , percent volume covered volume covered , percent 95.8 Non- 96.16 96.14 95.87 95.65 95.91 95.99 96.07 95.56 (%) coplanar

30Gy (P>0.05) in the beam-on time between the non-coplanar 95.91±0.21 95% (average, 6.2±1.3 min) and coplanar VMAT plans (average, 5.6±0.5 min). The results of the VMAT QA are shown in PTV V 96.7 95.7

95.83 95.78 95.88 95.66 96.71 96.01 95.46 Figure 3. The average gamma passing rates for the non- Coplanar

95.97±0.44 coplanar and coplanar VMAT QA with criteria of 3%/3 mm were 95.4%±2.6% and 95.6%±1.6%, respectively, which indicated good agreement between the calculated plan dose 25 Non- 26.24 25.72 25.03 25.04 25.72 25.67 25.99 25.04 and the measured dose. (Gy) coplanar 25.49±0.48 98%

Discussion PTV D , minimum dose to 98% volume; V 98% volume; , minimum dose to 25 26.69 25.61 25.04 25.33 25.46 25.54 26.72 25.74 98%

Coplanar Nevelsky et al. (13) evaluated the feasibility of the RTOG 25.68±0.63 0933 trial using the Elekta Infinity to perform IMRT with seven coplanar plus two non-coplanar beams. We hypothesized that VMAT could achieve the same results. In 32.8 Non- 33.06 34.99 33.69 33.64 33.07 32.94 33.55 33.44 coplanar (Gy) this study, we performed HA-WBRT using non-coplanar 33.46±0.68 2% and coplanar VMAT with Elekta Synergy. Our results

PTV D showed that for all VMAT plans, the hippocampal dose can

32.81 33.04 34.27 32.94 32.93 33.49 32.76 33.36 33.14 achieve the suggested criteria of the RTOG 0933 trial, with Coplanar 33.19±0.47 ; HI, homogeneity index; CI, conformity index. Dmax of the PTV (PTV Dmax) lower than 37.5 Gy, while maintaining the PTV coverage (at least 90% of the PTV by , maximum dose to 2% volume; D

2% the PD). Non- 92.91 92.66 93.21 93.69 93.15 92.92 93.03 92.82 92.48

(%) In comparison with the study of Nevelsky et al. (13), coplanar 92.99±0.35

30Gy their results showed that the average PTV D98% was

25.7 Gy, PTV D2% was 37.2 Gy, HI was 0.36, and Dmax of PTV V the hippocampus was 14.3 Gy, and our results showed that 91.6 93.36 91.73 93.83 92.29 92.72 93.04 92.89 91.68

Coplanar the average D of the hippocampus was slightly higher

92.57±0.80 max (14.9 Gy); however, our results showed better average PTV Dosimetric parameters for PTV SD D (33.46 Gy), PTV D (25.49 Gy), and HI (0.25). ± 2% 98% Gondi et al. (18) proposed 9-beam non-planar IMRT Table 5 Table Patient 1 2 3 4 5 6 7 8 9 Mean volume; D planning target PTV, dose by 95% of the prescribed covered with nine different couch angles for HA-WBRT, and their

Table 6 Gamma passing rate values (%) with different criteria (3%/3 mm, 2%/2 mm) and beam-on time 3%/3 mm 2%/2 mm Beam-on time (min) Patient Coplanar Non-coplanar Coplanar Non-coplanar Coplanar Non-coplanar

1 96.2 98.0 88.1 91.2 5.8 5.7

2 94.7 95.1 86.7 88.0 5.1 5.7

3 95.5 95.5 89.3 88.8 5.1 9.8

4 97.2 97.4 90.7 92.3 5.7 5.5

5 92.8 91.4 83.7 82.1 6.3 5.9

6 96.9 92.5 87.6 86.1 5.0 5.7

7 93.9 98.1 86.0 92.7 6.3 5.5

8 97.7 97.5 90.0 90.0 5.0 5.5

9 95.6 93.1 86.3 83.1 6.0 6.2

Mean ± SD 95.6±1.6 95.4±2.6 87.6±2.2 88.3±3.8 5.6±0.6 6.2±1.4

A Coplanar

B Non-coplanar

Figure 3 Calculated and measured dose profiles. (A) A coplanar VMAT planvs. (B) a non-coplanar VMAT plan for patient 7. Left: measured dose distributions. Middle: calculated dose distribution. Lower graph: comparison of the measured dose and calculated dose (solid line). The gamma passing rates (3%/3 mm) for the coplanar and non-coplanar VMAT plans were 93.9% and 98.1%, respectively. VMAT, volumetric- modulated arc therapy.

Table 7 Summary of dosimetric results for HA-WBRT (mean value) Optic Number of PTV PTV PTV Hippocampus Lens Study Technique HI chiasm patients V30Gy (%) D2% (Gy) D98% (Gy) D100% (Gy) Dmax (Gy) Dmax (Gy) Dmax (Gy)

Chen et al. 9 VMAT Coplanar 92.57 33.19 25.68 0.24 8.60 15.29 4.77 33.58

Non-coplanar 92.99 33.46 25.49 0.25 8.56 14.99 4.23 33.94

Nevelsky 10 IMRT Coplanar NA NA NA NA NA NA NA NA et al. (13) Non-coplanar 92 37.28 25.37 0.36 8.37 14.35 NA 35.97

Gondi 5 IMRT Coplanar NA NA NA NA NA NA NA NA et al. (18) Non-coplanar 93 NA NA 0.3 NA 15.3 3.8 NA

Krayenbuehl 10 VMAT Coplanar NA NA NA NA NA NA NA NA et al. (19) Non-coplanar 92 33.5 25.8 0.24 8.1 14.1 4.6 32.9

Wang 10 VMAT Coplanar 91.49 35.12 26.62 0.28 9.33 16 5.87 34.71 et al. (21) IMRT Non-coplanar 92.94 35.11 27.2 0.26 8.9 14.36 4.27 35.02

PTV, planning target volume; V30Gy, percent volume covered by 30 Gy; D2%, maximum dose to 2% volume, D98%, minimum dose to 98% volume; D100%, dose to 100% volume; Dmax, maximum dose; HI, homogeneity index.

results showed that the average Dmax of the hippocampus the high dose in the brain while maintaining PTV coverage. was 15.3 Gy, and the average HI was 0.3. Our non-coplanar As for the better Dmax and Dmin of the hippocampus in the

VMAT plans showed better average Dmax and HI values study of Krayenbuehl et al. (19), we believe that this can be than those of Gondi et al. (18), and the shorter treatment explained by the usage of a Trilogy linac (Varian Medical time for the non-coplanar VMAT of this study can be System, Palo Alto, CA, USA) with 60 MLC pairs of 0.5 cm expected due to less couch angle adjustment (0° and 70°). leaf width at isocenter. The narrower MLCs of the Trilogy Krayenbuehl et al. (19) evaluated the feasibility of HA- compared with the MLCs of the Elekta Synergy used in this WBRT according to the RTOG 0933 trial using an automated study can affect the treatment plan quality, since the width TPS with VMAT of two FAs and two non-coplanar PAs. of the MLC would affect the spatial resolution of the dose

Their results showed that for 10 patients, the average Dmax and distribution, and the penumbra width of the MLC could minimum dose (Dmin) of the hippocampus were 14.1 Gy (range, determine the dose fall-off in the hippocampal avoidance 12–15.3 Gy) and 8.1 Gy (range, 7.8–8.5 Gy), respectively; regions (20). the average PTV V30Gy and PTV Dmax were 92% and 36 Gy In the study performed by Wang et al. (21) using coplanar

(range, 35.1–36.5 Gy), respectively. In this study, we used the VMAT with two FAs, the average PTV D2% and PTV D98% same TPS as the study performed by Krayenbuehl et al. (19), were 35.1 and 26.6 Gy, respectively, and the Dmax and Dmin and our results for the non-coplanar VMAT plans showed that of the hippocampus were 16 and 9.3 Gy, respectively. In this the average Dmax and Dmin of the hippocampus were 14.9 Gy study, four FAs were used for the coplanar VMAT, which

(range, 13.8–15.8 Gy) and 8.5 Gy (range, 8.3–8.8 Gy). For allowed us to achieve better PTV D2%, PTV D98%, and Dmax the PTV, Krayenbuehl et al. (19) aimed to reduce the high and Dmin values of the hippocampus than those reported dose in the normal brain (i.e., PTV D2%), and the average by Wang et al. (21). Based on the results, we speculate that

PTV D2% of their study was 33.5 Gy. In our study, the increasing the arc number of VMAT could be used to easily average PTV D2% was 33.4 Gy. Although our study showed achieve the dose constraints of the RTOG 0933 trial but a higher average PTV coverage (92.9%) than that reported would increase the treatment time as well. The dosimetric by Krayenbuehl et al. (19) (92.0%), the Dmax and Dmin of comparison data from the studies mentioned above and our the hippocampus in our study were both higher than their study are summarized in Table 7. results but still met the criteria of the RTOG 0933 trial. For Dmax and Dmin of the hippocampus, our results Therefore, our results indicated that this study could reduce indicated that no significant differences were observed

© Therapeutic Radiology and Oncology. All rights reserved. Ther Radiol Oncol 2021;5:1 | http://dx.doi.org/10.21037/tro-20-50 Therapeutic Radiology and Oncology, 2021 Page 9 of 11 between the non-coplanar and coplanar VMAT plans. This study shows that the suggested criteria of the RTOG

For Dmax of the lens, the non-coplanar VMAT plans guidelines for the hippocampal dose can be achieved in both showed a significantly lower value than the coplanar non-coplanar and coplanar VMAT plans. The non-coplanar

VMAT plans. Previously reported of radiation-induced VMAT plans showed a significantly lower Dmax of the lens lens change in animal and human radiation cataract than the coplanar VMAT plans. However, for the doses to in radiation workers, exposure of the lens to ionizing other OARs, the coplanar VMAT plans showed comparable radiation can result in opacification (22). Nguyen et al. (23) results. In addition, better treatment efficiency for coplanar proposed a mean lens dose threshold of 7 Gy, and they VMAT than non-coplanar VMAT can be expected in reported that the cataract risk can be reduced to less than clinical practice due to the shorter beam-on time and fixed 25%. In addition, the National Council on Radiation couch angle. This study provides a dosimetric comparison Protection and Measurements No. 26 report suggests that of two different VMAT techniques for HA-WBRT, and we it is more advantageous to keep the lens doses as low as performed VMAT QA for each treatment plan to verify the possible according to the as low as reasonably achievable clinical feasibility. principle (24). The non-coplanar technique could decrease the D max Acknowledgments of the lens; however, due to the couch rotation during the treatment, the rotation accuracy for couch and gantry Funding: The authors disclosed receipt of the following needs to be assessed before the non-coplanar treatment. financial support for the research and publication of The difference in treatment managements in clinical this article: this work was supported by Taipei Medical practice between the coplanar and non-coplanar VMAT University - Shuang-Ho Hospital (grant number: plans results in the difference in delivery time. Although 107HCP-11). there was no statistically significant difference in the beam- on time between the non-coplanar (average, 6.2 min) Footnote and coplanar VMAT plans (average, 5.6 min). In clinical practice, however, coplanar VMAT is performed with a Reporting Checklist: The authors have completed the MDAR fixed couch angle, and the couch angle needs to be adjusted reporting checklist. Available at http://dx.doi.org/10.21037/ for the non-coplanar VMAT. Therefore, we believe that tro-20-50 the coplanar VMAT is less time-consuming than the non- coplanar VMAT. The shorter treatment time can reduce Conflicts of Interest: All authors have completed the ICMJE patient discomfort and decrease patient irritability during uniform disclosure form (available at http://dx.doi. treatment. org/10.21037/tro-20-50). All authors report grants from Because VMAT involves continuous gantry rotation Taipei Medical University - Shuang-Ho Hospital, outside and leaf motion with a varying dose rate, it is important to the submitted work. verify the consistency of the TPS and beam delivery. In this study, we performed VMAT QA for each treatment plan Ethical Statement: The authors are accountable for all to evaluate the feasibility of HA-WBRT. On average, the aspects of the work in ensuring that questions related gamma passing rate with criteria of 3%/3 mm was above to the accuracy or integrity of any part of the work are 90%, within the action level of 90% recommended by the appropriately investigated and resolved. The study was AAPM Task Group 119 report (25). The profile shown conducted in accordance with the Declaration of Helsinki in Figure 3 demonstrates that for the hippocampus, the (as revised in 2013). The study was approved by the Taipei measured dose distribution was in good agreement with the Medical University Joint Institutional Review Board calculated plan dose distribution. (TMU-JIRB No. N201711047), and informed consent was taken from all the patients

Conclusions Open Access Statement: This is an Open Access article The application of VMAT for HA-WBRT has been a trend distributed in accordance with the Creative Commons in clinical treatment for patients with brain metastases, and Attribution-NonCommercial-NoDerivs 4.0 International one advantage is the significant reduction in treatment time. License (CC BY-NC-ND 4.0), which permits the non-

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doi: 10.21037/tro-20-50 Cite this article as: Chen LJ, Li MH, Cheng HW, Kuo CY, Sun WL, Tsai JT. Hippocampus-sparing whole-brain radiotherapy: dosimetric comparison between non-coplanar and coplanar planning. Ther Radiol Oncol 2021;5:1.